Department of Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria.
Department Pharmacology, Physiology and Microbiology, Division Pharmacology, Karl Landsteiner University of Health Sciences, 3500 Krems, Austria.
Cells. 2020 Apr 1;9(4):855. doi: 10.3390/cells9040855.
Beyond their crucial role in hemostasis, platelets are increasingly recognized as regulators of inflammation. Via modulation of the immune system by direct and indirect interactions with leukocytes, platelets regulate several aspects of tumor-associated pathology. They influence inflammatory processes in cancer at various stages: platelets alter the activation status of the endothelium, recruit leukocytes to tumor sites and attune the inflammatory milieu at sites of primary and metastatic tumors. Patients with cancer show systemic changes of platelet activation. Tumor-associated platelet activation facilitates initiation of the coagulation cascade and constitutes a significant risk for thrombosis. Tumor-activated platelets further contribute to cancer progression by promoting critical processes such as angiogenesis and metastasis. Platelets modulate innate leukocyte effector functions such as antigen presentation by dendritic cells, monocyte recruitment and differentiation or neutrophil extracellular trap formation, which sculpture immune responses but also promote thrombosis and metastasis. On the other hand, responses of the adaptive immune system are also regulated by platelets. They are also involved in T-helper cell 17 differentiation, which represents a double-edged sword in cancer progression, as these cells propagate angiogenesis and immunosuppressive activities but are also involved in recruiting immune cells into tumors and stimulating effector CD8 T cells. Moreover, platelets fine-tune tumor surveillance processes by modulating natural killer cell-mediated cancer cell recognition and effector functions. This review aims at summarizing the role of platelet-leukocyte interactions in the development and progression of cancer and puts its focus on cancer-related alterations of platelet and leukocyte functions and their impact on cancer pathology.
除了在止血中发挥关键作用外，血小板也越来越被认为是炎症的调节剂。通过与白细胞的直接和间接相互作用来调节免疫系统，血小板调节与肿瘤相关的病理学的几个方面。它们在癌症的各个阶段影响炎症过程：血小板改变内皮细胞的激活状态，招募白细胞到肿瘤部位，并调节原发性和转移性肿瘤部位的炎症环境。癌症患者表现出系统性的血小板激活变化。肿瘤相关的血小板激活促进了凝血级联的启动，并构成了血栓形成的重大风险。肿瘤激活的血小板通过促进血管生成和转移等关键过程进一步促进癌症的进展。血小板调节先天白细胞效应功能，如树突状细胞的抗原呈递、单核细胞募集和分化或中性粒细胞细胞外陷阱的形成，这些功能塑造免疫反应，但也促进血栓形成和转移。另一方面，适应性免疫系统的反应也受到血小板的调节。它们还参与辅助性 T 细胞 17 的分化，这在癌症进展中是一把双刃剑，因为这些细胞促进血管生成和免疫抑制活性，但也参与招募免疫细胞进入肿瘤并刺激效应 CD8 T 细胞。此外，血小板通过调节自然杀伤细胞介导的癌细胞识别和效应功能来微调肿瘤监测过程。这篇综述旨在总结血小板-白细胞相互作用在癌症发展和进展中的作用，并重点关注与癌症相关的血小板和白细胞功能的改变及其对癌症病理学的影响。
